POS0715 SUSTAINED REMISSION FROM WEEKS 16 TO 52 AND WEEKS 24 TO 52 IN PATIENTS TREATED WITH SARILUMAB: POST-HOC ANALYSIS OF SAPHYR TRIAL IN PATIENTS WITH POLYMYALGIA RHEUMATICA
Authors: B. Dasgupta, A. Praestgaard, S. Fiore, K. Ford, J. Sloane Lazar, A. Dua, R. Spiera
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The SAPHYR study (NCT03600818) in patients with polymyalgia rheumatica (PMR) who were resistant to glucocorticoid (GC) taper met the primary endpoint with a significantly higher proportion of patients in the sarilumab arm versus the comparator arm achieving sustained remission from weeks 12 to 52 (28.3% vs 10.3%; P=0.0193) <sup>[1]</sup>. Sarilumab, when administered to patients with rheumatoid arthritis at a dose of 200 mg subcutaneously, achieved a steady state within 14 to 16 weeks <sup>[2]</sup>. Patients treated with sarilumab in SAPHYR may not have reached steady state concentrations by week 12 when disease remission was assessed for the primary endpoint of sustained remission. <h3>Objectives</h3> This post-hoc analysis of the SAPHYR study assessed the proportion of patients achieving sustained remission up to week 52 from week 16 and from week 24. <h3>Methods</h3> Patients were randomized (1:1 ratio) to 52 weeks of treatment with sarilumab 200 mg every 2 weeks (Q2W) + 14 week GC tapered regimen (sarilumab arm) or placebo Q2W + 52 week GC tapered regimen (comparator arm). Here, we assessed the proportion of patients achieving sustained remission and each of the sustained remission components from week 16 and from week 24 to the end of study. Sustained remission was defined as having met all of the following: disease remission at 16 weeks and 24 weeks (no PMR signs and symptoms + CRP normalization [&lt;10 mg/L]); absence of disease flare from weeks 16 to 52 and weeks 24 to 52; sustained reduction of CRP (to &lt;10 mg/L, with no successive elevations to ≥10 mg/L) from weeks 16 to 52 and weeks 24 to 52; and successful adherence to protocol specified GC taper dose from weeks 16 to 52 and weeks 24 to 52. Patients who did not achieve remission, received rescue treatment with open label prednisone (or equivalent), withdrew from the study before week 52, or had missing data that prevented assessment of the primary endpoint were considered as non-responders. <h3>Results</h3> Between Oct 2018 and Jul 2020, 60 patients were randomized to the sarilumab arm and 58 patients to the comparator arm (intent to treat population). A higher proportion of patients in the sarilumab arm, versus the comparator, achieved sustained remission from weeks 16 to 52 (30.0% vs 8.6%; difference [95% CI]: 21.4 [7.7, 35.0]; P=0.0047) and from weeks 24 to 52 (31.7% vs 10.3%; difference [95% CI]: 21.3 [7.2, 35.5]; P=0.0063). This improvement in sustained remission rate in the sarilumab arm was due to additional responses seen between weeks 12 to 24 <b>(Figure 1</b>). Similarly, all the independent components of the sustained remission were achieved by a higher proportion of patients in the sarilumab arm, versus the comparator arm, during each assessment period. In both the sarilumab arm and the comparator arm, the disease remission rates decreased slightly at weeks 16 and 24 compared with week 12; sarilumab arm 40.0% and 41.7%, respectively vs 46.7% and comparator arm 31.0% and 20.7%, respectively vs 37.9%. Disease remission rates declined due to missing or abnormal CRP, as the proportion of patients with no PMR signs and symptoms increased over time. In the sarilumab arm, the proportion of patients with no disease flare increased from weeks 12 to 52 assessment to weeks 16 to 52 and weeks 24 to 52 assessments, whereas the proportion of patients with sustained CRP normalization or those who adhered to protocol-defined GC taper remained the same during the three assessment periods <b>(Figure 1).</b> Safety data were consistent with the know profile of sarilumab and were presented previously <sup>[1]</sup>. <h3>Conclusion</h3> This post-hoc analysis showed that a higher proportion of patients in the sarilumab arm, versus the comparator arm, achieved sustained remission when assessed from week 16 and week 24 up to week 52. Most patients who achieved sustained remission did so rapidly by week 12 with some additional responses seen between week 12 and 24. <h3>Reference</h3> [1]Dasgupta B, et al. <i>Ann Rheum Dis.</i> 2022;81:210-211; <sup>2</sup>McCarty D &amp; Robinson A. <i>Ther Adv Musculoskelet Dis</i>. 2018; 10(3): 61–67. <h3>Acknowledgements</h3> Scientific writing support was provided by Vijay Kadasi of Sanofi. <h3>Disclosure of Interests</h3> Bhaskar Dasgupta Speakers bureau: Cipla and Roche Chugai, Consultant of: Roche Chugai and Sanofi, Grant/research support from: Abbvie, Roche Chugai, and Sanofi, Amy Praestgaard Shareholder of: Sanofi, Employee of: Sanofi, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Jennifer Sloane Lazar Shareholder of: Sanofi, Employee of: Sanofi, Anisha Dua Consultant of: Abbvie, Sanofi, Chemocentryx, and Novartis, Robert Spiera Consultant of: GSK, Regeneron, Abbvie, Sanofi, Chemocentryx, Novartis, Galderma, Vera, Chemomab, Boehringer Ingelheim, and BMS, Grant/research support from: Roche-Genetech, Astra-Zeneca, GSK, Kadmon, Boehringer Ingelheim, Chemocentryx, Corbus, Formation Biologics, Novartis, Inflarx, and Principia.